Although it is well established that both pharmacological and psychological therapies are relatively effective in treating chronic posttraumatic stress disorder (PTSD), the recent Institute of Medicine (IOM, 2007) report highlights vast gaps in our current knowledge noting a lack of knowledge regarding factors influencing treatment acceptance and completion, the combined effectiveness of these pharmacological and psychological treatment, and their efficacy in common subpopulations (e.g., those with diagnostic co-occurrence). To address these gaps, we propose the first large-scale trial to directly focus on individualizing PTSD care across several key parameters: choice of treatment, the effects of combined psychotherapy and pharmacological PTSD treatment, and the presence of co-occurring major depression. Building on our previous psychotherapy and pharmacotherapy trial on PTSD treatment, we will conduct a doubly randomized preference trial in which female and male trauma survivors with chronic PTSD will be randomly assigned to either choice or no choice treatment conditions. In the choice condition, patients will choose between prolonged exposure (PE) and prolonged exposure plus sertraline (PE + SER). In the no choice condition, patients will be randomly assigned to either prolonged exposure alone (PE) or prolonged exposure plus sertraline (PE + SER). In addition, we will specifically recruit and examine patients with co-occurring major depressive disorder (MDD). Outcome, as measured by both psychopathology and broader functioning measures, will be assessed at post-treatment and through 24-month follow-up. We will also examine biopsychosocial markers of response, psychotherapy change processes, and cost-effectiveness of these treatments. The Specific Aims are: 1) To compare the short-term and long-term effectiveness of PE to that of PE + SER;2) To systematically compare patients who have chosen their treatment to those who have not in terms of treatment adherence, treatment completion, and effectiveness;and 3) To compare individuals with PTSD alone to those with PTSD and co-occurring major depression. In line with the NIMH's strategic plan, this application focuses on more personalized medicine, focusing on patients'choices and better understanding individual trajectories of outcome.